Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transport ATPases can be lumped into four distinct types, P, F, V, and ABC, with the first three designated 20 years ago (Pedersen, P.L. and Carafoli, E., Trends Biochem. Sci. 12, 146-150, 1987) and the ABC type included more recently. The mini-reviews (>20) that comprise this volume of the Journal of Bioenergetics and Biomembranes describe work presented at the 2007 FASEB Conference (6th) on Transport ATPases (Kathleen Sweadner, Chair; Rajini Rao, Co-Chair). Since these conferences began in 1997, the "transport ATPase field" has seen tremendous progress. Advances include a much better understanding of the structure, mechanism, and regulation of each of the four major ATPase types as well as their physiological and medical relevance. In fact, the transport ATPase field has entered a new era in which work on these enzymes is likely to contribute to new therapies for multiple diseases that affect both people and animals. Among these are cancer and heart disease, mitochondrial diseases, osteoporosis, macromolecular degeneration, immune deficiency, cystic fibrosis, diabetes, ulcers, nephro-toxicity, hearing loss, skin disorders, lupus, and malaria. In addition, as several members of the transport ATPase family include those involved in drug resistance their study may help alleviate this recurring problem in drug development. Finally, the transport ATPase field is also paving the way for nanotechnology focused on nano-motors with work on the F-type ATPases (F(0)F(1)) leading the way. These ATPases driven in reverse by a proton gradient have the capacity to interconvert electrochemical energy into mechanical energy and finally into chemical energy conserved in the terminal bond of ATP. In mammalian mitochondria these events occur on a larger complex or "nano-machine" called the "ATP synthasome" that consists of the ATP synthase in complex formation with carriers for P(i) and ADP/ATP.
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PMID:Transport ATPases into the year 2008: a brief overview related to types, structures, functions and roles in health and disease. 1817 9

The birth and mortality rates in the Democratic Republic of Congo (DRC), a former Belgian colony, are high, i.e., 48.9/1000 and 17/1000 respectively. The DRC also has one of the highest maternal death rates in the world, i.e., 1289/100,000 live births. Health conditions have not improved since independence. Access to drinking water is limited, living conditions are poor, and food availability in households is low. The mean health services utilization rate in the DRC is estimated to be 0.15 visits/inhabitant/year. The incidence of transmissible diseases is rising. This increase is observed even for illnesses that were under control before independence such as sleeping sickness, onchocerciasis, leprosy, and tuberculosis. One the main causes of mortality and morbidity in the population is malaria that is responsible for the deaths of 150,000 to 250,000 children under the age of 5 every year. The HIV prevalence rate is 4.5% with 1.19 million persons with AIDS and 930,000 orphans whose parents died of AIDS. Other potentially epidemic diseases including bubonic plaque and Ebola hemorrhagic fever are serious threats. Non-transmissible diseases are also on the rise including diabetes, systemic arterial hypertension, cancer and neglected diseases such as sickle cell anemia. To meet these challenges, the country's health authorities have established a program called the Strategy for Reinforcement of the Health System (SRHS). One goal of the SRHS is to develop health zones in order to improve access to quality health care for the whole population.
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PMID:[Medicine and health in the Democratic Republic of Congo: from Independence to the Third Republic]. 1822 27

Thomas Jefferson, the third President of the USA, was often the victim of a panoply of disorders including episodic headaches, dysentery, rheumatism, multiple bone fractures, malaria, possibly tuberculosis, dental problems, diabetes and urinary tract obstruction. Intermittently he experienced anxiety, depression and insomnia; he was an anxious, striving perfectionist, a compulsively controlled man.
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PMID:The medical history of Thomas Jefferson (1743-1826). 1846 85

Haptoglobin is an acute phase protein that scavenges haemoglobin in the event of intravascular or extravascular haemolysis. The protein exists in humans as three main phenotypes, Hp1-1, Hp2-2 and Hp2-1. Accumulated data on the protein's function has established its strong association with diseases that have inflammatory causes. These include parasitic (malaria), infectious (HIV, tuberculosis) and non-infectious diseases (diabetes, cardiovascular disease and obesity) among others. Phenotype-dependent poor disease outcomes have been linked with the Hp2-2 phenotype. The present review brings this association into perspective by looking at the functions of the protein and how defects in these functions associated with the Hp2 allele affect disease outcome. A model is provided to explain the mechanism, which appears to be largely immunomodulatory.
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PMID:Haptoglobin, inflammation and disease. 1848 67

While circulating levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1) have been associated with diverse conditions including myocardial infarction, stroke, malaria, and diabetes, comprehensive analysis of the common genetic determinants of sICAM-1 is not available. In a genome-wide association study conducted among 6,578 participants in the Women's Genome Health Study, we find that three SNPs at the ICAM1 (19p13.2) locus (rs1799969, rs5498 and rs281437) are non-redundantly associated with plasma sICAM-1 concentrations at a genome-wide significance level (P<5x10(-8)), thus extending prior results from linkage and candidate gene studies. We also find that a single SNP (rs507666, P = 5.1x10(-29)) at the ABO (9q34.2) locus is highly correlated with sICAM-1 concentrations. The novel association at the ABO locus provides evidence for a previously unknown regulatory role of histo-blood group antigens in inflammatory adhesion processes.
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PMID:Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women. 1860 67

The pivotal role of proteases in many diseases has generated considerable interest in their basic biology, and in the potential to target them for chemotherapy. Although fundamental to the initiation and progression of diseases such as cancer, diabetes, arthritis and malaria, in many cases their precise role remains unknown. Activity-based chemical proteomics-an emerging field involving a combination of organic synthesis, biochemistry, cell biology, biophysics and bioinformatics-allows the detection, visualisation and activity quantification of whole families or selected sub-sets of proteases based upon their substrate specificity. This approach can be applied for drug target/lead identification and validation, the fundamentals of drug discovery. The activity-based probes discussed in this review contain three key features; a 'warhead' (binds irreversibly but selectively to the active site), a 'tag' (allowing enzyme 'handling', with a combination of fluorescent, affinity and/or radio labels), and a linker region between warhead and tag. From the design and synthesis of the linker arise some of the latest developments discussed here; not only can the physical properties (e.g., solubility, localisation) of the probe be tuned, but the inclusion of a cleavable moiety allows selective removal of tagged enzyme from affinity beads etc. The design and synthesis of recently reported probes is discussed, including modular assembly of highly versatile probes via solid phase synthesis. Recent applications of activity-based protein profiling to specific proteases (serine, threonine, cysteine and metalloproteases) are reviewed as are demonstrations of their use in the study of disease function in cancer and malaria.
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PMID:Activity based chemical proteomics: profiling proteases as drug targets. 1869 Aug 89

Glycogen synthase kinase-3, a serine/threonine kinase, has been implicated in a wide variety of pathological conditions such as diabetes, Alzheimer's disease, stroke, bipolar disorder, malaria and cancer. Herein we report 3D-QSAR analyses using CoMFA and CoMSIA and molecular docking studies on 3-anilino-4-phenylmaleimides as GSK-3alpha inhibitors, in order to better understand the mechanism of action and structure-activity relationship of these compounds. Comparison of the active site residues of GSK-3alpha and GSK-3beta isoforms shows that all the key amino acids involved in polar interactions with the maleimides for the beta isoform are the same in the alpha isoform, except that Asp133 in the beta isoform is replaced by Glu196 in the alpha isoform. We prepared a homology model for GSK-3alpha, and showed that the change from Asp to Glu should not affect maleimide binding significantly. Docking studies revealed the binding poses of three subclasses of these ligands, namely anilino, N-methylanilino and indoline derivatives, within the active site of the beta isoform, and helped to explain the difference in their inhibitory activity.
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PMID:Glycogen synthase kinase-3 inhibition by 3-anilino-4-phenylmaleimides: insights from 3D-QSAR and docking. 1883 67

Extracts of 42 medicinal plants used for the treatment of anaemia, diabetes, AIDS, malaria and obesity were screened for phytochemical substances and antioxidant potentials. The plant extracts were prepared as hydrolysed (for total antioxidant) and non-hydrolysed (for free antioxidant). Extracts were analysed using three different assay methods for antioxidant analysis: Folin (Folin Ciocalteu reagent), FRAP (Ferric Reducing Antioxidant Power) and DPPH (1,1-diphenyl-2-picrylhydrazyl). The leaves of Alchornea cordifolia showed the highest antioxidant properties as determined by both Folin and FRAP free antioxidant, followed by Dacryodes edulis and Ocimum basilicum in FRAP and by Dacryodes edulis, Harungana madagascariensis for Folin and DPPH method. For total antioxidant activity, Alchornea cordifolia was ranked first followed by Dacryodes edulis, Harungana madagascariensis, Ocimum basilicum for the FRAP method while for the Folin method Harungana madagascariensis occupied the first position followed by Cylicodiscus gabunensis, Ocimum basilicum, Coleus coprosifolius, Alchornea cordifolia, Dacryodes edulis. All the plants show some antioxidant activity irrespective of the method used. The phytochemical studies revealed the presents of important bioactive constituents with antioxidant activity that may have some medicinal properties.
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PMID:Medicinal plants can be good source of antioxidants: case study in Cameroon. 1906 32

The aim of this review is to provide the reader general and inspiring prospects on recent and promising fields of innovation in oral drug delivery. Nowadays, inventive drug delivery systems vary from geometrically modified and modular matrices, more close to "classic" pharmaceutical manufacturing processes, to futuristic bio micro-electro-mechanical systems (bioMEMS), based on manufacturing techniques borrowed from electronics and other fields. In these technologies new materials and creative solutions are essential designing intelligent drug delivery systems able to release the required drug at the proper body location with the correct release rate. In particular, oral drug delivery systems of the future are expected to have a significant impact on the treatment of diseases, such as AIDS, cancer, malaria, diabetes requiring complex and multi-drug therapies, as well as on the life of patients, whose age and/or health status make necessary a multiple pharmacological approach.
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PMID:Novel platforms for oral drug delivery. 1913 14

Management of women's health seldom includes cardiovascular disease (CVD) prevention in spite of CVD being the most common cause of death in females being even more common than cancer, HIV/AIDS, malaria and tuberculosis combined. According to the World Heart Federation, CVD is indisputably the most serious, neglected health problem for women in both the developing and the developed worlds. A possible reason may be that CVD has traditionally been perceived as a 'man's illness'. Since 6 out of 10 deaths from CVD can be prevented, it is of utmost importance that there is more general awareness about CVD in women. The most important factors for developing CVD are dyslipidaemia, hypertension, smoking, stress, diabetes, obesity (especially abdominal fat distribution), physical inactivity, poor eating habits and possibly excessive alcohol intake. Some unique risk factors for CVD exist in women; of which older age at presentation is a major one as they are more likely to suffer from co-morbidities such as diabetes and hypertension.
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PMID:Risk factors for cardiovascular disease in women. 1940 46


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